A tyrosine repressor is known to negatively regulate biosynthesis of aromatic amino acids such as tyrosine. Further, the structure of the tyrosine repressor gene of Escherichia coli has already been elucidated (E. C. Cornish et al., J. Biol. Chem., 261, 403-410 (1986)).
L-DOPA is a precursor of dopamine, which is a nerve transmitter substance, and useful as a therapeutic agent for Parkinson's disease and so forth. L-DOPA has conventionally been manufactured by chemical synthesis. In recent years, however, L-DOPA is enzymatically synthesized from pyrocatechol and serine, or pyrocatechol, pyruvate and ammonia by using tyrosine phenol lyase.
Tyrosine phenol lyase is known to be produced by a wide variety of microorganisms belonging to the genus Escherichia, Pseudomonas, Flavobacterium, Bacillus, Serratia, Xanthomonas, Agrobacterium, Achromobacter, Aerobacter, Erwinia, Proteus, Salmonella, Citrobacter, Enterobacter or the like (Japanese Patent No. 2521945, Japanese Patent Publication (Kokoku) No. 6-98003). Its enzymatic characteristics have also been elucidated (Biochem. Biophys. Res. Commun., 33, 10 (1963)).
There were reported a structural gene and nucleotide sequence of an upstream region of tyrosine phenol lyase gene of bacteria belonging to the genus Erwinia known to highly express tyrosine phenol lyase (H. Suzuki et al., J. Ferment. Bioeng., 75, No.2, 145-148 (1993)). Moreover, the inventors of the present invention successfully isolated a gene coding for a tyrosine repressor from the aforementioned bacteria and disclosed that the tyrosine repressor had positive regulatory activity for expression of the tyrosine phenol lyase gene (Japanese Patent Laid-Open Publication (Kokai) No. 11-313672).
It was also reported that the mtr and tyrP+4 promoters were activated about two times by substitution of a glycine residue for aspartic acid residue at a position of 97 and substitution of a phenylalanine residue for the aspartic acid residue at a position of 117 in the Escherichia coli tyrR gene (J. Bacteriol., 178, 1120-1125 (1996)).